Classical zinc-dependent histone deacetylase (HDAC) (HDAC)

Classical zinc-dependent histone deacetylases (HDACs) are a family of 11 enzymes that catalyze the removal of acetyl groups from lysine residues on both histone and non-histone proteins (UniProt, 2024). These enzymes are categorized into three classes based on their homology to yeast proteins: Class I (HDAC1, 2, 3, and 8), Class II (HDAC4, 5, 6, 7, 9, and 10), and Class IV (HDAC11) (NCBI Gene, 2024). By deacetylating histones, they promote a condensed chromatin state, which typically leads to the repression of gene transcription (PubMed: PMC7400110). Beyond epigenetics, they regulate the function of numerous cytoplasmic proteins involved in the cell cycle, apoptosis, and DNA repair (StatPearls: NBK559020). In many cancers, HDACs are overexpressed or aberrantly recruited to promoters, leading to the silencing of tumor suppressor genes (NIH National Cancer Institute, 2023). Pharmacological inhibition of these enzymes has proven effective in treating certain hematological malignancies by inducing cell cycle arrest and programmed cell death (FDA, 2024).

Other names

Zinc-dependent histone deacetylasesClassical HDACsHistone deacetylase family (Classes I, II, and IV)Metal-dependent HDACs

Inhibition of the zinc-dependent catalytic site of HDAC enzymes, preventing the removal of acetyl groups from lysine residues on histones and non-histone proteins, which results in hyperacetylation, chromatin relaxation, and the reactivation of silenced genes (StatPearls, 2023; PubMed: PMC3436371).